진단 시 낮은 종양 분율에 의해 유전 검사 위음성을 보인 급성 백혈병 1예: 최신 진단 기준에 비춘 시사점
A Case of False Negative Genetic Assessment in Acute Leukemia Due to Low Tumor Fraction at Diagnosis: Its Implications under the New Diagnostic Criteria
2
조회
0
다운로드
0
인용
0
참고문헌
키워드
초록
급성 백혈병에서 유전 변이를 정확하게 검출하는 것은 매우 중요하다. 간혹 종양 분율이 진단 시 높지 않은 경우, 유전 검사에서 위음성이 초래될 수 있다. 본 증례는 B림프모구백혈병에서 초진 시 골수 흡인 검체에 모세포가 7.1%로 낮았던 예이다. 초진 시의 핵형분석 및 차세대염기서열분석 결과는 음성으로 분석되었었다. 그러나 후향적으로 검토할 때, 재발 시에 검출된 변이 중 일부가 초진 시에도 매우 낮은 분율로 존재했던 것을 확인하였다. 최근 개정된 급성 백혈병에 대한 WHO 및 International Consensus Classi cation의 진단 기준을 고려할 때, 초진 시 골수 내 모세포의 분율이 낮은 경우들은 더 많아질 것으로 예상된다. 본 증례는 이러한 종양 분율이 낮은 급성 백혈병에 대해, 위음성을 줄임으로써 환자의 정확한 진단과 치료에 기여하기 위한 노력들이 필요함을 시사한다.
Abstract
The accurate detection of genetic mutations is very important in acute leukemia. Occasionally, tumor fraction may not be high at diagnosis, thus leading to false negative genetic test results. We present a case of acute lymphoblastic leukemia with relapse where the percentage of blasts in bone marrow aspirate was only 7.1% at the initial diagnosis. Karyotyping and next-generation sequencing results appeared negative at diagnosis; however, a retrospective review of the initial tests revealed that some of the mutations detected later at relapse were present even at the initial diagnosis but at very low fractions. Given the recently revised World Health Organization classification (fifth edition) and International Consensus Classification, the probability of encountering acute leukemia with a low blast percentage in bone marrow is expected to increase. This case indicates that efforts should be made to reduce false negative assessments for low tumor fraction leukemia to obtain a more accurate diagnosis and improve treatment.
참고문헌 (10)
- Borowitz MJ, "WHO classification of tumours of haematopoietic and lymphoid tissues", pp.200~ (2017), IARC
- Arber DA, "WHO classification of tumours of haematopoietic and lymphoid tissues", pp.130~ (2017), IARC
- Khoury JD, "The 5th edition of the World Health Organization classification of haematolymphoid tumours : myeloid and histiocytic", dendritic neoplasms, 2022, pp.36, 1703~1719
- Arber DA, "International consensus classification of myeloid neoplasms and acute leukemias : integrating morphologic, clinical, and genomic data", Blood, 140, pp.1200~1228 (2022)
- Forero-Castro M, "Integrated genomic analysis of chromosomal alterations and mutations in B-cell acute lymphoblastic leukemia reveals distinct genetic profiles at relapse", Diagnostics(Basel), 10, pp.455~ (2020)
- Nashed AL, "Clinical applications of BCR-ABL molecular testing in acute leukemia", J Mol Diagn, 5, pp.63~72 (2003)
- Kim J, "The use of technical replication for detection of low-level somatic mutations in next-generation sequencing", Nat Commun, 10, pp.1047~ (2019)
- Lee KS, "Analytical and clinical validation of cell-free circulating tumor DNA assay for the estimation of tumor mutational burden", Clin Chem, 68, pp.1519~1528 (2022)
- de Boer EN, "Detection of fusion genes to determine minimal residual disease in leukemia using next-generation sequencing", Clin Chem, 66, pp.1084~1092 (2020)
- Chen H, "Minimal residual disease detection by next-generation sequencing of different immunoglobulin gene rearrangements in pediatric B-ALL", Nat Commun, 14, pp.7468~ (2023)